Sequence information
Variant position: 717 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 770 The length of the canonical sequence.
Location on the sequence:
SNKGAIIGLMVGGVVIATVI
V ITLVMLKKKQYTSIHHGVVE
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human SNKGAIIGLMVGGVVIATVI-V ITLVMLKKKQYTSIH-HGVVE
Chimpanzee SNKGAIIGLMVGGVVIATVI-V ITLVMLKKKQYTSIH-HGV
Mouse SNKGAIIGLMVGGVVIATVI-V ITLVMLKKKQYTSIH-HGV
Rat SNKGAIIGLMVGGVVIATVI-V ITLVMLKKKQYTSIH-HGV
Pig SNKGAIIGLMVGGVVIATVI-V ITLVMLKKKQYTSIH-HGV
Caenorhabditis elegans SASSVFQPYVLASAMFITAICI IAFAITNARRRRAM--RGF
Drosophila EGRNVYFTLSFAGIALMAAV-F VGVAVAKWRTSRSPHAQGF
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
18 – 770
Amyloid-beta precursor protein
Chain
672 – 770
C99
Chain
688 – 770
C83
Chain
691 – 770
C80
Chain
712 – 770
Gamma-secretase C-terminal fragment 59
Chain
714 – 770
Gamma-secretase C-terminal fragment 57
Transmembrane
702 – 722
Helical
Region
695 – 722
Interaction with PSEN1
Site
704 – 704
Implicated in free radical propagation
Site
706 – 706
Susceptible to oxidation
Modified residue
729 – 729
Phosphothreonine
Modified residue
730 – 730
Phosphoserine; by APP-kinase I
Alternative sequence
306 – 770
Missing. In isoform APP305.
Mutagenesis
704 – 704
G -> V. Reduced protein oxidation. No hippocampal neuron toxicity.
Mutagenesis
706 – 706
M -> L. Reduced lipid peroxidation inhibition.
Mutagenesis
706 – 706
M -> V. No free radical production. No hippocampal neuron toxicity.
Mutagenesis
717 – 717
V -> CS. Unchanged amyloid-beta protein 42/total amyloid-beta ratio.
Mutagenesis
717 – 717
V -> K. Decreased amyloid-beta protein 42/total amyloid-beta ratio.
Mutagenesis
717 – 717
V -> M. Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage.
Mutagenesis
728 – 728
Y -> A. No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion.
Literature citations
A system for studying the effect(s) of familial Alzheimer disease mutations on the processing of the beta-amyloid peptide precursor.
Denman R.B.; Rosenzcwaig R.; Miller D.L.;
Biochem. Biophys. Res. Commun. 192:96-103(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 655-737; VARIANTS AD1 GLY-717; ILE-717 AND PHE-717;
A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.
Murrell J.R.; Farlow M.; Ghetti B.; Benson M.D.;
Science 254:97-99(1991)
Cited for: VARIANT AD1 PHE-717;
Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations.
Liepnieks J.J.; Ghetti B.; Farlow M.; Roses A.D.; Benson M.D.;
Biochem. Biophys. Res. Commun. 197:386-392(1993)
Cited for: VARIANTS AD1 ILE-717 AND PHE-717;
Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene.
Farlow M.; Murrell J.; Ghetti B.; Unverzagt F.; Zeldenrust S.; Benson M.D.;
Neurology 44:105-111(1994)
Cited for: VARIANT AD1 PHE-717;
Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor protein are specific for the increased secretion of A beta 42(43).
Maruyama K.; Tomita T.; Shinozaki K.; Kume H.; Asada H.; Saido T.C.; Ishiura S.; Iwatsubo T.; Obata K.;
Biochem. Biophys. Res. Commun. 227:730-735(1996)
Cited for: CHARACTERIZATION OF VARIANTS AD1 GLY-717; ILE-717 AND PHE-717; MUTAGENESIS OF VAL-717;
Disclaimer:
Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.